This project proposes building controlled single-walled carbon nanotube (SWNT) arrays at the wafer scale toi obtain large arrays of nanosensor devices and use them to detect biological molecules in solutions with a focus on protein detections. Specific aims will include, (1) Construction and testing of nanotubes/nanowire sensors with aptamer or antibody based recognition of protein via combined electronic and fluorescence detections for and on the sensor array devices. (2) Development of bio-molecule multiplexing strategies for nanotube/nanowire sensor arrays in solution phase without drying the proteins or antibodies on the arrays to prevent protein denaturing. (3) Use both fluorescence detection and SWNT or NW transistor electrical detection scheme to explore the pros and cons for each method. (4) Develop multiplexing methods using electrical and/or electrochemical control of each device in a sensor array. This will enable multiplexing without drying of proteins and afford high density protein nano-arrays. The spatial chemical resolution will then be controlled electrically, an unique feature for electrically active sensors such as SWNTs and nanowires. (5) Testing of nanowire arrays with mouse serum samples. (5) Testing of nanowire arrays with human serum samples of cancer patients. (6) Close collaboration between nano-scientists (Dai), oncologists and clinic experts (Felsher, Utz). The nanosensor arrays will be closed compared with existing protein micro-array technology to identify key advantages of nanosensors and develop nanoscale tools and sensing platforms that can solve key problems in microarrays. We expect the advantages will include electrical control of chemical immobilization and multiplexing, high density, arraying without drying for proteins and electrical transistor sensing scheme. The bio-functionalized nanotube-sensor chips will be used for detecting antibody-antigen binding, ligand- or peptide-protein binding. The specific systems that will be used for the nanosensor development will be streptavidin with biotin for year 1, tenascin-C with aptamer and antibody probes for year 2-3 and Her-kinase patterns with aptamter and antibody probes for year 3-5. In comparison to nanowire sensing research in other groups, the key uniqueness of our project is that first, we are inclusive of using optical fluorescence detection for nanosensors in addition to electrical detection. We will use the electrical degree of freedom for biomolecular multiplexing and sensing. Secondly, we have protein microarray expert in our team and the outcome of our research project will be to enable a nanotechnology significantly more advanced than the current micro-arrays. Thirdly, we will use large numbers of nanotubes and nanowires for each sensor site in the array to build redundancy, reduce background noise and optimize sensitivity. All of the reported nanowire sensors thus far use a single nanowire for each sensing site and has high noise and low stability.